|Twin to twin transfusion syndrome and
monochorionic twinning European network
Twin-Twin Transfusion Syndrome (TTTS): a complication of identical twinsIn a number of identical twin pregnancies blood may pass disproportionately from one baby to the other through connecting blood vessels in their shared placenta. If this imbalance occurs early in pregnancy and is left untreated, it is likely to cause loss of both babies. Until recently, the only available treatment consisted in repeated drainage of excess amniotic fluid with less than optimal results. Therefore a new, more cause-oriented approach was introduced where a surgical separation of the connecting vessels on the placenta is performed by means of laser. This technique is currently evaluated.
Even for modern medicine, twins still pose major problems. Although twins represent only a small fraction of pregnancies, they are responsible for a large proportion of problems in new-borns. Twins are also at increased risk of death before or just after birth. One specific problem in identical twins is the Twin-Twin Transfusion Syndrome (TTTS), which only occurs in identical twins who share the same afterbirth or placenta (monochorionic twins). Since they share their placenta, they also share their blood flow. In 15 % of monochorionic twins, an unequal distribution of blood supply develops between both babies leading to TTTS. If TTTS presents early in pregnancy (before 26 weeks) and no treatment is attempted, it has a mortality rate of over 80% and can be the cause of severe handicaps for the few survivors.
A shared placentaThere are two types of twin pregnancies:
The Twin-TwinTransfusion SyndromeIn identical twins sharing a single placenta (monochorionic), there will almost invariably be blood vessels that connect the blood circulations of both babies. This will cause no problems, as long as the distribution of blood supply between the babies is well balanced. However, it sometimes happens that more blood is directed from one baby towards the other. The first baby is called then the donor since he essentially pumps his blood into the second baby, who is called the recipient.
The donor usually suffers from anaemia (too little blood), hypovolemia (too little fluid) and is frequently smaller. Due to a deficiency in blood and fluid, the donor will produce less urine. Since urine is the main constituent of the amniotic fluid, the amniotic fluid around the donor will decrease (oligohydramnion), eventually disappearing altogether. The donor will appear to be almost shrink-wrapped and ‘stuck’ up against the wall of the womb, which explains why the donor is often called the ‘stuck twin’. Meanwhile, the recipient has his own worries. He receives too much blood and eliminates the excess fluid by increasing his urine production. This causes too much amniotic fluid around the recipient (polyhydramnion) and a rapid and excessive distension of the womb, leading to a too early delivery or rupture of the membranes (Fig.1). TTTS is thus essentially a disease of the placenta, since the twins themselves are normal. However, unborn babies are fully dependent on the placenta for oxygen and food supply and disease of the placenta will invariably affect their wellbeing.
The condition is called Twin-Twin Transfusion Syndrome (TTTS) because:
TTTS complicates about 15% of identical twin pregnancies. If TTTS occurs before 26 weeks gestational age (the normal duration of pregnancy is 40 weeks), it will have dramatic implications. It is estimated that the chance of survival is less than 1 in 5. Sometimes one of the babies dies in the womb. Unfortunately this doesn’t solve the problem. The death of one twin causes an abrupt fall of its blood pressure and the surviving twin may literally pump all its blood (exsanguinate) into the deceased twin’s circulation. Therefore, it is not unusual that the surviving twin dies too, shortly after the first one. Furthermore, of fetuses that survive this acute phase, approximately 25% will sustain severe damage of the brain, liver, kidneys or other organs.
DetectionThe single most important fact that needs to be determined early in a twin pregnancy is whether the twins are monochorionic (sharing the same placenta) or dichorionic. Only an early ultrasound scan (before 14 weeks) can reliably establish this, since later on in pregnancy obtaining a clear image of the separating membranes and the single placenta becomes more difficult. Determination of chorionicity is essential, since it identifies monochorionic twins, who are at increased risk of adverse outcome and require careful follow-up. TTTS will develop in 15% of these monochorionic twins, whereas it virtually never develops in dichorionic twins. If monochorionic twins are diagnosed, ultrasound scans should be performed at regular intervals, preferentially fortnightly, in an attempt to diagnose TTTS at an early stage. The telltale signs are often different-sized babies, different-sized bladders, and too little fluid in one sac and too much in the other. These features are present even before the mother becomes symptomatic; e.g. before she experiences abdominal distension, breathlessness and contractions. Once the diagnosis of TTTS is made, appropriate treatment can be instituted.
Amniotic fluid drainageThis treatment involves the draining of excess amniotic fluid through a needle that is passed into the sac of the recipient. The exact mechanism through which amniodrainage improves the outcome of TTTS is unclear. Probably the reduced pressure in the womb after amniodrainage improves blood supply towards the babies. Amniodrainage certainly alleviates the discomfort of the mother associated with carrying excess fluid and reduces the risk of a too early delivery. Although amniodrainage is a simple and safe technique, it does not affect the underlying cause of the condition; the unbalanced blood distribution and its consequences persist. Furthermore, amniotic fluid often increases again, necessitating one or more repeat intervention(s) in the majority of cases. Using amniodrainage as treatment for TTTS, both babies survive in 48 % of cases, at least one baby survives in 70% of cases and there is loss of both babies in 30% of cases. However, approximately 20% of survivors sustain some form of brain damage.
Laser treatmentLaser treatment is a relatively new technique (more widely introduced in 1995), which aims to rectify the source of the problem. The procedure involves visualisation and separation the connecting blood vessels on the placenta by means of laser energy. A tiny “endoscope” is introduced in the womb through a small cut in the abdomen in order to identify the responsible blood vessels on the placenta (Fig.2). Subsequently, these vessels are coagulated and interrupted by means of a laser beam (Fig.3). At the end of the procedure, the excess amniotic fluid is evacuated until normal levels. In over 95% of cases, the amniotic fluid volume remains steady during the rest of pregnancy. This indicates that laser treatment does something different than amniodrainage and may tackle the cause of the disease. Another indication is the fact that after laser treatment only about 6% of babies sustain some form of brain damage. This is significantly less than after serial amniodrainages, where this is approximately 20%. At an older age, it may be that this figure increases to around 10 %; unfortunately for amniodrainage there are no figures available for comparison. Using laser as treatment for TTTS, both babies survive in 54% of cases, at least one baby survives in at least 80% of cases and there is loss of both babies in 20% of cases. It may appear that survival is better after laser treatment than after amniodrainage, however this difference is not large enough to be what is called statistically significant.
Tiny instrumentsFetoscopy stands for looking (in Greek skopein) at the unborn baby (fetus) in the womb. For such an operation very small instruments are used. Hence the scope, through which the doctor looks inside the womb, is 1.2 to 2 mm wide, comparable to the ink container of a ballpoint. The scopes are connected to a video camera, so that the operation can be followed on a television screen. The scope is brought into the womb via a special, leak proof cannula. This cannula is passed through a small cut (about 3 to 5 mm) in the abdomen. Through this cannula other instruments can be introduced, such as the laser fibre, small forcepses or scissors and small tubes for irrigation or the drainage of amniotic fluid. Where exactly in the abdomen this cannula is introduced, depends on the location of the placenta and the position of the unborn babies.
Amniodrainage versus laser treatment
It is too early to say for certain which treatment is to be
preferred. Data of the late 1990s indicate that the survival
rates are comparable. The interventions themselves both carry
risks. In about 15% of laser interventions, one baby dies shortly
after the intervention, usually the smallest baby. It has been
suggested that the piece of placenta this baby keeps after the
separation is too small to survive. In comparison, amniodrainage
is associated with a nearly 30 % risk for both babies to die
(albeit not so closely in time after the procedure). TTTS remains
a complex and serious condition and at present it is difficult to
weigh both treatments against each other. Therefore in order to
answer this question, a trial has been set up in Europe. The idea
that laser treatment may bring down the risk of brain damage from
20% to 6% at birth was the most important incentive for this
trial and the study will focus on demonstrating that difference
rather than showing a difference in survival rates.
Putting things in perspectiveThe news that unborn babies or their placentas can be operated in the womb has been received with some criticism. ‘Are these experiments and are they really necessary?’ is a frequently heard remark. Operative interventions on the unborn baby are indeed quite new; at least in the way they are presently performed. However, years of preparatory work have preceded its introduction in clinical practice. Furthermore, some other procedures on the unborn baby have already gained widespread acceptance. It is also difficult to appreciate the benefit of such an intervention, but couples who are confronted with problems such as TTTS obviously wish to have healthy children and an intervention is literally of vital importance. ‘Save our child’ is the very question they ask their doctor.
As previously mentioned, untreated TTTS is fatal for both babies in 80 to 100% of cases. At present, the most commonly used treatment is the evacuation of excess amniotic fluid at regular intervals. However, this method has only average results, since still too many babies die and of those who survive, an important number remains handicapped. In this perspective, it is certainly justified to strive for newer and better treatments. That is where laser is positioned and experience with it is growing fast.
However, this does not imply that such a new technique should be accepted without criticism. On the contrary, it is our duty to improve the existing techniques in order to help more people. At the moment, both treatment methods for TTTS are being evaluated in a trial generated by a research group funded by the European Commission. Information about this group and the study is available on the Internet (www.eurotwin2twin.org). This site is primarily for doctors who wish to collaborate in this trial, but is also accessible for the public. At present, patients with TTTS are asked to participate in the trial and following randomisation (like flipping a coin), they are assigned to either amniodrainage or laser therapy. This is the only way we can truly evaluate which therapy is the best.
If you feel uncomfortable participating to the above quoted study, that is no problem, and this will not affect at all the attitude of your doctors. In that case, we would still like you to consider consenting to store data on this pregnancy. Information of patients who do not wish to participate in the randomised trial is as valuable and is currently collected in the so-called “observational study”. Permission to store data on TTTS pregnancies will be asked by doctors contributing to this study in a similar fashion as for the study above.
Note: This text was written by scientists from the Eurofoetus research consortium and will be updated at regular intervals. Recent updates are best obtained via the website: www.eurotwin2twin.org.
Figure1: Schematic drawing of TTTS. The smaller fetus is the donor, who has almost no amniotic fluid and is stuck to the wall of the womb, whereas the larger fetus is the recipient, who has too much amniotic fluid. Both babies share a single placenta.
Figure 2: Drawing of the shared placenta in TTTS. Multiple vessels connect both fetuses over what is called “anastomoses” (open circles). These anastomoses are the subject of laser coagulation.
Figure 3: Illustration of a fetoscopic laser treatment. A cannula has been placed through the abdominal wall, through which a scope and laser beam has been passed. The connecting vessels are identified and subsequently destroyed.
Figures: K Dalkowski, with permission of Karl Storz Endoskope.